The Temple Thrombosis Research Center is a formally established research institute within the medical school dedicated to advancing our understanding of the etiology, pathogenesis, diagnosis and treatment of arterial and venous thrombosis. In the SCOR, investigators in this center are examining the role of platelets, plasma coagulation factors, vascular wall cells, and neutrophils in thrombogenesis. As normal biochemical and physiological mechanisms are elucidated, departures from these patterns of response provide the knowledge of pathological processes that are necessary for development of appropriate diagnostic tests. The increasing understanding of the abnormalities underlying the thrombotic process makes possible the rational development of therapeutic interventions to inhibit or prevent thrombogenesis in a vessel. Each project in the present proposal has the potential to indicate an appropriate inhibitory drug or other therapeutic approaches to prevent platelet aggregation, fibrin formation or the consequences of vessel wall injury, all of which contribute to the formation of an obstructing thrombus. We have divided the research activities of this SCOR into three areas corresponding to three broad research objectives. The first objective (A) is to study the interaction of the cell and molecular biology of contract system activation and inhibition which encompasses the projects of Drs. Colman and Schmaier on kininogen and C1 inhibitor. The second goal is to investigate two major aspects of platelet function, coagulant activity and calcium modulation, as reflected in the projects of Drs. Walsh and Rao. The third task is to elucidate the mechanism of action of naturally occurring inhibitors, the arginine serpins and the disintegrins, including the investigations of Drs. Bock and Niewiarowski. The supporting core units A-C represent common facilities for protein structure led by Dr. Jameson, administrative organization supervised by Dr. Colman, and research resources under the aegis of Dr. Stewart.